The cohesin complex is best known for its role in sister chromatid cohesion. Over the past few years, it has become apparent that cohesin also regulates gene expression, but the mechanisms by which it does so are unknown. Recently, three groups mapped numerous cohesin-binding sites in mammalian chromosomes and found substantial overlap with the CCCTC-binding factor (CTCF).1–3 CTCF is an insulator protein that blocks enhancer–promoter interactions, and the investigators found that cohesin also contributes to this activity. Thus, these studies demonstrate at least one mechanism by which cohesin can control gene expression. BioEssays 30:715–718, 2008. © 2008 Wiley Periodicals, Inc.